Tulobuterol has a bronchodilating action by selectively stimulating .beta..sub.2 receptor of the sympathetic nerve. Thus, it has been widely used for treating chronic bronchitis, bronchial asthma and the like in an attempt to reduce dyspnea of patients with respiratory tract stricture.
Tulobuterol is generally administered into the body by oral administration using, for example, tablets and the like. This method, however, is associated with the problems of difficulty confronted in administering to infants and the like, emergence of side effects caused by a steep increase in blood concentration of the drug, short duration of drug effect, and the like. To solve these problems, there have been developed percutaneous absorption type preparations containing various drugs to administer the drug into the body through the skin surface. With respect to tulobuterol, Japanese Patent Unexamined Publication No. 5-194202 (LTS Lohmann Therapie Systeme), Japanese Patent Unexamined Publication No. 5-238953 (Zambon Group S.p.A), Japanese Patent Unexamined Publication No. 7-285854 (Nitto Denko Corporation) and Japanese Patent Examined Publication No. 7-25669 (Nitto Denko Corporation) propose percutaneous absorption type preparations thereof.
These publications mostly relate to a preparation containing tulobuterol in a plaster layer in a concentration of not less than solubility of the drug in an adhesive, wherein tulobuterol is partially dispersed in the plaster layer in a crystalline state. In general, a higher concentration of a drug dissolved in a plaster layer is considered to lead to a higher percutaneous absorption rate of the drug, and a higher content of a drug in a plaster layer is considered to lead to a longer duration of drug release. However, keeping a drug in a dissolution state at a high concentration stably in a polymer used to form a plaster layer is generally difficult to achieve. For satisfactory percutaneous absorption rate and sustained release of a drug, therefore, the drug is contained in a plaster layer at a high concentration of not less than the solubility of the drug in an adhesive and part of the drug is present in a crystalline state in the plaster layer, as disclosed in the above-mentioned prior art publications.
A preparation containing solid drug crystals in the plaster layer is susceptible to precipitation of the drug crystals on the surface of the plaster layer where it comes into contact with the skin, thus degrading the adhesive property to the skin. Inasmuch as the diffusion rate of the drug molecule in the polymer is strikingly slower than that in a liquid, the drug crystals do not precipitate quickly in the plaster layer. Gradual crystallization of the drug in the plaster layer is expected to influence the adhesive property of the preparation to the skin and drug releasing property with the lapse of time. When the drug is contained at a concentration of not less than the solubility thereof in the adhesive, the preparation containing part of the drug in a crystalline state in the plaster layer may fail to provide sufficient stability of the preparation quality. This poses a high threshold in achieving superior percutaneous absorption, long duration of the efficacy and superior adhesion to the skin, of the preparation.